Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers.

ABSTRACT: Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function in viral replication as an integral component of the ribonucleoprotein complex, associating with viral RNA and polymerase within the viral core. The multifunctional nature of NP makes it an attractive target for antiviral intervention, and inhibitors targeting this protein have recently been reported. In a parallel effort, we discovered a structurally similar series of influenza replication inhibitors and show that they interfere with NP-dependent processes via formation of higher-order NP oligomers. Support for this unique mechanism is provided by site-directed mutagenesis studies, biophysical characterization of the oligomeric ligand:NP complex, and an X-ray cocrystal structure of a

SUBMITTER: Gerritz SW 

PROVIDER: S-EPMC3174639 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature